chr6-43572565-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020750.3(XPO5):c.241G>A(p.Gly81Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0023 in 1,613,814 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 27 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 24 hom. )

Consequence

XPO5
NM_020750.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.69

Variant links:

Genes affected

XPO5 (HGNC:17675): (exportin 5) This gene encodes a member of the karyopherin family that is required for the transport of small RNAs and double-stranded RNA-binding proteins from the nucleus to the cytoplasm. The encoded protein translocates cargo through the nuclear pore complex in a RanGTP-dependent process. [provided by RefSeq, Aug 2011]

XPO5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026955009).

BP6

Variant 6-43572565-C-T is Benign according to our data. Variant chr6-43572565-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 787830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (1627/152150) while in subpopulation AFR AF= 0.0363 (1507/41496). AF 95% confidence interval is 0.0348. There are 27 homozygotes in gnomad4. There are 757 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1627 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPO5	NM_020750.3 link	c.241G>A	p.Gly81Ser	missense_variant	Exon 3 of 32	ENST00000265351.12	NP_065801.1	Q9HAV4
XPO5	NR_144392.2 link	n.415G>A		non_coding_transcript_exon_variant	Exon 3 of 33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
XPO5	ENST00000265351.12 link	c.241G>A	p.Gly81Ser	missense_variant	Exon 3 of 32	1	NM_020750.3	ENSP00000265351.7	Q9HAV4
XPO5	ENST00000398799.2 link	n.*92G>A		non_coding_transcript_exon_variant	Exon 3 of 4	4		ENSP00000381779.2	E2QRM3
XPO5	ENST00000398799.2 link	n.*92G>A		3_prime_UTR_variant	Exon 3 of 4	4		ENSP00000381779.2	E2QRM3

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1628

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0364

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00472

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000417

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00314

AC:

783

AN:

249244

Hom.:

AF XY:

0.00271

AC XY:

366

AN XY:

135228

show subpopulations

Gnomad AFR exome

AF:

0.0364

Gnomad AMR exome

AF:

0.00403

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000434

Gnomad OTH exome

AF:

0.00429

GnomAD4 exome

AF:

0.00142

AC:

2077

AN:

1461664

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

945

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.0367

Gnomad4 AMR exome

AF:

0.00461

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000362

Gnomad4 OTH exome

AF:

0.00318

GnomAD4 genome

AF:

0.0107

AC:

1627

AN:

152150

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

757

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0363

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000417

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.00261

Hom.:

Bravo

AF:

0.0121

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0301

AC:

118

ESP6500EA

AF:

0.000481

AC:

ExAC

AF:

0.00377

AC:

456

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000830

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 22, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.050

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0027

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.4

PrimateAI

Benign

0.34

PROVEAN

Benign

1.4

REVEL

Benign

0.051

Sift

Benign

0.59

Sift4G

Benign

0.82

Polyphen

0.0

Vest4

0.11

MVP

0.043

MPC

0.37

ClinPred

0.0029

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.065

gMVP

0.074

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over